Chemoprophylactic Activity of M5717 in PfSPZ Challenge Model

November 7, 2023 updated by: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

A Phase Ib, Randomized, Double-Blind, Placebo Controlled, Sequential Study of Single Oral Doses of M5717 to Explore the Chemoprophylactic Activity of M5717 in a Controlled PISPZ Challenge Model in Healthy Participants

The main purpose of this study was to assess the chemoprophylactic activity and dose-exposure-response relationship of single oral dose of M5717 administered after direct intravenous inoculation (DVI) of Plasmodium falciparum sporozoite (PfSPZ) challenge in healthy participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Leiden, Netherlands
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Participants who are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
  • Participants who have a body weight within 50 to 100 kilograms (kg) and body mass index within the range 19.0 to 29.9 kilograms per meter square (kg/m2) (inclusive)
  • Male participants, during the study intervention period and for at least 120 days after the day of the study intervention dose (covering a full sperm cycle of 90 days starting after 5 half lives of last dose of study intervention: - refrain from donating sperm plus, either - abstain from intercourse with a woman of childbearing potential (WOCBP) or - use a male condom, when having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of less than (<) 1 percent (%) per year, since a condom may break or leak
  • Female participants who are: - not a WOCBP; - at least 1 year post-menopausal (amenorrhea greater than or equal to [>=] 12 months and follicle-stimulating hormone [FSH] >= 40 milli-international units per milliliter [mIU/mL]) at screening; - surgically sterile (bilateral oophorectomy, hysterectomy or bilateral salpingectomy; tubal ligation alone is not sufficient)
  • Participants who are capable of giving signed informed consent, which includes compliance with the requirements (including mandatory intake of rescue medication to participants who have been administered the investigational Plasmodium falciparum sporozoite challenge) and restrictions listed in the informed consent form (ICF) and this protocol
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with 12-Lead electrocardiogram (ECG) outside normal range (QTcF greater than [>] 450 milli seconds [ms], pulse rate [PR] > 215 ms, or QRS > 120 ms) and deemed clinically relevant by the Investigator
  • Supine systolic blood pressure > 140 or < 90 millimeter of mercury (mmHg), diastolic blood pressure > 90 or < 50 mmHg, and pulse rate > 90 or < 50 beats per minute (min) at screening and at admission on Day -1 (any abnormal blood pressure or pulse rate results may be repeated once and if the repeat result is within the normal range, it is not considered to have met the exclusion criterion)
  • Seropositive for human immunodeficiency virus (HIV) I and II antibody or antigen), hepatitis B virus (HBV; hepatitis B surface antigen [HBsAg]), or hepatitis C virus (HCV; antibody) tests
  • Liver function tests above the upper limit of normal (ULN) (> 3 x ULN) the day before DVI / study intervention administration (Day -1)
  • History or presence of diagnosed food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue medications to be used in the study), or history of anaphylaxis or other severe allergic reactions
  • Participant with a whole blood donation or loss of > 450 mL within 60 days before administration of study drug or unwilling to defer blood donations for 6 months
  • Other protocol defined exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Early liver stage: Pooled Placebo
Participants received single dose of placebo matched to M5717 capsule on Day 1 after 2 hours of Plasmodium falciparum Sporozoite (PfSPZ) (3200 sporozoites per injection) intravenous (IV) inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: Palcebo
Participants received single oral dose of placebo matched to M5717 capsule on Day 1.
Experimental: Early liver stage: 30 mg M5717
Participants received single dose of M5717 30 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 30 mg
Participants received 30 mg single oral dose of M5717 capsule on Day 1.
Experimental: Early liver stage: 60 mg M5717
Participants received single dose of M5717 60 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 60 mg
Participants received 60 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 60 mg
Participants received 60 mg single oral dose of M5717 capsule on Day 5.
Experimental: Early liver stage: 80 mg M5717
Participants received single dose of M5717 80 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 80 mg
Participants received 80 mg single oral dose of M5717 capsule on Day 1.
Experimental: Early liver stage: 100 mg M5717
Participants received single dose of M5717 100 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 100 mg
Participants received 100 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 100 mg
Participants received 100 mg single oral dose of M5717 capsule on Day 5.
Experimental: Early liver stage: 200 mg M5717
Participants received single dose of M5717 200 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 200 mg
Participants received 200 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 200 mg
Participants received 200 mg single oral dose of M5717 capsule on Day 5.
Experimental: Late liver stage: Pooled Placebo
Participants received single dose of placebo matched to M5717 capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: Placebo
Participants received single oral dose of placebo matched to M5717 capsule on Day 5.
Experimental: Late liver stage: 60 mg M5717
Participants received single dose of M5717 60 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 60 mg
Participants received 60 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 60 mg
Participants received 60 mg single oral dose of M5717 capsule on Day 5.
Experimental: Late liver stage: 100 mg M5717
Participants received single dose of M5717 100 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 100 mg
Participants received 100 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 100 mg
Participants received 100 mg single oral dose of M5717 capsule on Day 5.
Experimental: Late liver stage: 200 mg M5717
Participants received single dose of M5717 200 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1.
Biological: PfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
Drug: M5717 200 mg
Participants received 200 mg single oral dose of M5717 capsule on Day 1.
Drug: M5717 200 mg
Participants received 200 mg single oral dose of M5717 capsule on Day 5.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Early Liver Stage: Number of Participants Over Time With Positive Parasitemia
Time Frame: Early Liver Stage: From Day 1 up to Day 28
Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge.
Early Liver Stage: From Day 1 up to Day 28
Late Liver Stage: Number of Participants Over Time With Positive Parasitemia
Time Frame: Late Liver Stage: From Day 5 up to Day 32
Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge.
Late Liver Stage: From Day 5 up to Day 32
Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR)
Time Frame: Early Liver Stage: From Day 1 up to Day 28
Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (>=) 100 asexual parasites per milliliter (mL) of blood.
Early Liver Stage: From Day 1 up to Day 28
Late Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR)
Time Frame: Late Liver Stage: From Day 5 up to Day 32
Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (>=) 100 asexual parasites per milliliter (mL) of blood.
Late Liver Stage: From Day 5 up to Day 32
Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth
Time Frame: Early Liver Stage: From Day 1 up to Day 28
Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI.
Early Liver Stage: From Day 1 up to Day 28
Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth
Time Frame: Late Liver Stage: From Day 5 up to Day 32
Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI.
Late Liver Stage: From Day 5 up to Day 32
Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score
Time Frame: Early Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26 and 28
The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here.
Early Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26 and 28
Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score
Time Frame: Late Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30 and 32
The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here.
Late Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30 and 32
Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model
Time Frame: From Day 5 up to Day 32
Exposure efficacy relationship was analyzed using logistic regression model. Different exposure matrices (AUC0-24, AUC0-168, AUC0-inf, C24 and C168) were analyzed using logistic regression model.
From Day 5 up to Day 32

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs
Time Frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE was defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention.
Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity
Time Frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Severity of adverse events (AE) were assessed by the investigator per the Qualitative Toxicity Scale. Grade 1= Mild, Grade 2=Moderate, Grade 3=Severe. The number of participants that experienced at least one solicited local TEAE were summarized by grade. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of participants with Grade=1, Grade=2 and 3 were reported.
Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Time Frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant changes from baseline in laboratory values which were deemed clinically significant by the investigator were reported.
Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Vital signs included oral body temperature, height, weight, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant changes from baseline in Vital signs which were deemed clinically significant by the investigator were reported.
Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Time Frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Single 12-lead ECG was obtained as outlined using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals. Number of participants with clinically significant changes from baseline in ECG which were deemed clinically significant by the investigator were reported.
Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated blood concentration at the last sampling time point at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured blood concentrations of the terminal log-linear phase.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Area under the blood concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12 and 24 hours post-dose
AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Pre-dose, 0.5, 1, 2, 3, 6, 12 and 24 hours post-dose
Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120 and 168 hours post-dose
AUC from time zero to 168 hours post dose. Calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120 and 168 hours post-dose
Maximum Observed Blood Concentration (Cmax) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Cmax was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Blood Concentration at 24 Hours (C24) of M5717
Time Frame: At 24 hours post-dose
Blood samples for PK analysis of C24 of M5717 was reported.
At 24 hours post-dose
Blood Concentration at 168 Hours (C168) of M5717
Time Frame: At 168 hours post-dose
C168 is the calculated blood concentration at 168 hours post-dose at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ).
At 168 hours post-dose
Time to Reach Maximum Blood Concentration (Tmax) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Apparent Terminal Half-life (t1/2) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Elimination Rate Constant (Lambda z) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Elimination rate constant determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Apparent Total Body Clearance From Blood (CL/f) of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from blood, CL= Dose/AUC0-inf
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717
Time Frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z).
Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 17, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 18, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 18, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 29, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 31, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS201618_0003
  • 2019-003414-14 (EudraCT Number)
  • 203481/Z/16/Z (Other Grant/Funding Number: Wellcome Trust)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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